RU2277915C2 - Method of raising antioxidant potential of selenium-containing aqueous solutions - Google Patents

Abstract

FIELD: pharmaceutical industry.

SUBSTANCE: invention concerns use of selenit-containing solution stabilized with pharmaceutically acceptable acids selected from citric acid, acetic acid, malic acid, carbonic acid, and mixtures thereof to prepare external-use drugs applicable to prophylaxis and treatment of herpes virus caused infections, in particular herpes simplex or nevus pigmentosis infections. Drug is provided in the form of gel or emulsion with pH value below 7.0, more favorably below 5.0, in particular 3.0-2.5.

EFFECT: increased herpes treatment efficiency, lack of toxicity, and increased bioavailability.

4 cl, 2 tbl, 3 ex

Description

FIELD OF THE INVENTION

The invention relates to medicine, to a method for increasing the antioxidant potential of selenium-containing aqueous solutions, as well as to selenium preparations pharmaceutically acceptable or compatible with food products.

State of the art

All metabolic processes in organic living creatures (plants, animals, people) in the sense of growth, differentiation and energy processes are, in the biochemical aspect, an alternation of reduction and oxidation processes. Such redox processes are ultimately the expression of the electronic transfer of biochemical reduction equivalents, such as NADH + H ⁺ (electron donor), to atmospheric molecular oxygen as an oxidizing agent (electron acceptor). The oxidation of our nutrients (fats, carbohydrates, proteins, salts) serves to constantly preserve and develop our biological structures.

However, on the other hand, it is our cellular and subcellular structures, tissues and organs formed from them, and ultimately each organic individual in their entirety consists precisely of those structures (nutrients) that are constantly supplied from the outside to preserve and develop living organisms are oxidized with the formation of energy and which, however, must simultaneously serve to preserve the functional, anatomical and histological structures. Consequently, these biological structures are ultimately also oxidizable, like those nutrients that must be oxidized to maintain our vital energy. To prevent the "self-oxidation" of biological structures, an organic living organism uses endogenous or exogenous "antioxidants." Endogenous antioxidants include, but are not limited to, enzymes and enzyme systems such as superoxide dismutase, catalase, peroxidase, cholesterol and reduced glutathione, and exogenous antioxidants are, for example, vitamin A, carotene B, vitamin E, vitamin C or selenium.

The degree of "antioxidant ability", i.e. the readiness to transfer electrons to other atoms and molecules is quantitatively expressed through the so-called "reduction potential" (standard redox potential). The table below provides an overview of the standard redox potentials of some endogenous and exogenous antioxidants of organic living things.

Standard Redox Potentials of Some Nutrients E ₀ (Volt) System +0.82 O ₂ / N ₂ O +0.366 (alkaline environment) Selenite +0.300 tocopherol (vitamin E) +0,100 ubiquinone (coenzyme Q ₁₀ ) +0.08 vitamin C +0 (+0.16 to -0.02 V) Flavonoid -0.12 riboflavin (vitamin B ₂ ) -0.22 cystine / cysteine -0.23 G SH / GSSG -0.29 lipoic acid (α-lipoic acid) -0.32 NADH + H ⁺ / NAD -0.740 (acidic environment) Selenite

Thus, atoms and molecules act as antioxidants (for the human body, first of all, nutrient molecules and enzyme complexes), which react with metabolic radicals faster than biological structures. Therefore, they protect our cellular and gene structures, as well as the structures of connective tissues as a result of the fact that they capture metabolic products (free radicals, peroxides) before they act, for example, on the unsaturated acids of our biomembranes or sulfur-containing elements of vital structural or enzyme proteins. As follows from the above table, certain elements, for example selenium, change their standard redox potential when the pH of the medium changes, and these compounds dissolve.

Selenium is an essential trace element for highly developed animals and people. It has a protective function for proteins from oxidation caused, for example, by glutathione peroxidase containing the amino acid selenocysteine in the active center. Selenium deficiency causes rheumatism and cataracts. Keshan disease, common in parts of China, is thought to be due to a lack of selenium. Selenites can increase the effect of vitamin E and neutralize mercury and cadmium poisoning. It is also believed that selenium has a protective effect against carcinogens.

On the other hand, selenium in high concentrations is toxic, and toxicity is due to the fact that it is able to displace sulfur from proteins. Excretion occurs, as a rule, in the form of selenate through the kidneys and intestines. Diseases of the human body occur when the daily food contains selenium in an amount of more than 1 μg / g (this requires a minimum content of selenium in an amount of 0.02 μg / g in order to prevent the phenomena caused by its deficiency). In total, the human body contains about 10-15 micrograms of selenium.

Also, in animals, poisoning phenomena occur when the selenium content in their feed is in an amount of more than 5-10 μg / g, for example, growth retardation, hair loss, softening of horns and hooves, feather loss in birds. However, selenium is also necessary for animals for raising chickens, turkeys and pigs, as well as for the prevention of specific diseases of useful animals, in particular sheep. Therefore, it is required to use sodium selenite or sodium selenate as an additive in mixed feed or for fertilizing pastures, since the natural content of selenium in animal and vegetable feeds is often insufficient or the element is excreted insufficiently.

SUMMARY OF THE INVENTION

The objective of the present invention is to improve selenium-containing preparations, ensuring their use in food and feed technology, as well as in pharmaceuticals and increasing their effect in these areas.

This problem is solved according to the invention using a method of increasing the antioxidant potential of selenium-containing aqueous solutions, characterized in that pharmaceutically acceptable or food-compatible acids are mixed into the selenium-containing aqueous solution.

It was found that a decrease in the pH of selenium-containing solutions, in particular solutions of sodium selenite / sodium selenate, leads, in comparison with solutions in which the pH is not reduced, to a strong increase in the antioxidant potential. The solutions prepared in accordance with the invention also found unexpected therapeutic effects, especially for diseases caused by free radicals and peroxides.

Therefore, it is preferable to use a solution of selenite or selenate as a selenium-containing aqueous solution.

As means for acidifying the selenium-containing solution, in particular, such agents are used that are compatible for humans and animals, for example, citric, acetic, malic, carbonic acids, various fruit acids and mixtures thereof.

The present invention also relates to a preparation comprising:

- a pharmaceutically acceptable or food compatible form of selenium in the form of selenite or selenate,

- a pharmaceutically acceptable or food-compatible acid selected from the range of: citric, acetic, malic, carbonic acids, various fruit acids and mixtures thereof.

The preparation according to the invention has an increased antioxidant potential, as a result of which it possesses properties that are positive for humans and animals when used in food / feed technology. In the framework of the pharmaceutical use of selenium compounds by means of the preparation according to the invention, the pharmaceutical effect is also increased or even new possibilities for the pharmaceutical use of selenium compounds are opened up.

It is preferable to set the acidification of the selenium-containing agent to a pH of less than 7.0, more preferably less than 5.0, in particular less than 4.0. Particularly preferred agents according to the invention have a pH of 6.0-2.0, in particular 3.0-2.5.

In the form of a preparation according to the invention, selenium is provided in the form of selenite or selenate. However, dimethyl selenide, selenomethionine, selenocysteine, or mixtures of these species are also suitable for various purposes.

The preparation according to the invention can be used not only in the form of an aqueous solution. Preferred additional forms are a gel form or emulsion, which have excellently proven themselves, in particular when used for pharmaceutical purposes, since local topical application becomes possible with their help.

It goes without saying that the preparation according to the invention may also contain auxiliary substances, such as buffering agents, colorants, stabilizers, carrier substances and / or other effective components, for example antibiotics, antiviral agents, antifungal agents, painkillers or anti-inflammatory agents wherein said excipients can be used in all possible combinations. The appropriate type of excipient or effective component is determined by the appropriate purpose in each case.

The preparation according to the invention is particularly suitable for pharmaceutical use. It is also preferable to use it as a food product, or as an additive in a food product, or as a feed, or as an additive to it.

When the pharmaceutical use of the preparation according to the invention was unexpectedly revealed, first of all, its effectiveness in the prevention and treatment of diseases caused by peroxides and radicals.

Therefore, it is preferable to use the preparation according to the invention for the preparation of a medicament for the prophylaxis or treatment of viral diseases, mainly herpes infections, in particular vesicle infections. On the other hand, the preparation according to the invention was extremely effective in the prevention and treatment of age spots (caused by deposits of lupofuscin).

The invention is explained in more detail with the help of the following examples, to which it, of course, is not limited.

Example 1. Preparation of an acidified sodium selenite solution

An acidified sodium selenite solution was prepared as follows (g per 100 ml):

sodium selenite pentahydrate 0,111 maltodextrin 0.5 lemon flavor 0.1 lemon acid 0.5 food coloring 0.01 potassium sorbate 0.1 sodium benzoate 0.05 distilled water 99.29

Example 2. The treatment of infections of vesicular lichen

Twelve adult patients (seven women and five men), as well as eight children (four girls and four boys) were treated with a diagnosis of stomatitis with herpes manifestations / small ulcers. The course consisted of taking five drops in the mouth five times a day (children received a solution diluted ten times) with simultaneous external treatment (five times a day, the affected areas were treated with a cotton swab moistened with drops) usually for seven days. Seven out of eight children additionally received local anesthetics and / or antibiotics and / or antifungal agents and / or painkillers and anti-inflammatory drugs for antioxidant selenium therapy; no additional antiviral treatment was prescribed.

Nine out of twelve adults were treated exclusively with potent antioxidant selenium drops, and one out of twelve patients received antiviral medication (Acyclovir) in addition to the drops. The results are presented in the table below.

Treatment for vesicular lip deprivation Patient No. Floor Frequency Previous treatment Side effects Treatment success one husband. once a year Topical ointment treatment Are absent one 2 husband. monthly Acyclovir Are absent one 3 husband. 3 to 5 times a year Acyclovir Are absent one four wives 3 times a year Acyclovir Are absent one 5 husband. - - - one 6 wives 3 times a year Famvir Are absent 2 7 wives monthly Acyclovir Are absent one 8 wives 3 to 5 times a year Acyclovir Are absent one 9 wives 3 times a year Acyclovir Are absent one 10 wives 3 times a year Acyclovir Are absent one

Stomatitis with herpes manifestations / small ulcers Patient No. Floor Frequency Previous treatment Side effects Treatment success eleven husband. Xylocain (Xylocaine) Are absent one 12 wives - - Are absent 2 13 wives - - Are absent one fourteen husband. - - Are absent one fifteen husband. - - Are absent one 16 wives - - Are absent 2 17 husband. - - Are absent one eighteen wives - - Are absent 2 19 wives - - Are absent 2 twenty husband. monthly - Are absent 2

At the same time, they mean:

1 - very good

2 - good

3 - not enough.

From the reports of the research results of the doctor who conducted these studies, it follows that in nineteen out of twenty cases, excellent therapeutic success (the disappearance of itching, cure of the vesicles) was achieved after 3-7 days. In those patients who suffered from relapses of herpes, after oral and external use of drops, there was a noticeable decrease in the number of relapses (prolongation of the intervals between relapses) or a complete disappearance of relapses compared with treatment with Acyclovir.

Example 3. The treatment of age spots

Pigment spots (the so-called senile spots) are the result of intensive deposition of protein, fatty acid and lipid membrane structures destroyed by free radicals and peroxides in the subcutaneous tissue and appear as locally limited areas near the pin head from light brown to dark brown in color. Three adult patients (two women and one man) used the described selenium drops (five times a day, up to ten drops were applied to the affected areas and rubbed with the back of the arm) for two months. As a result of the application, a marked decrease in the number of age spots or lightening of dark age spots was noted.

Claims (4)

1. The use of a selenite-containing solution stabilized with pharmaceutically acceptable acids selected from citric, acetic, malic, and carbonic acids, fruit acids, and mixtures thereof, for the preparation of an external medicine for the prevention or treatment of herpes virus infections, in particular vesicular lichen infections. 2. The use of a selenite-containing aqueous solution stabilized with pharmaceutically acceptable acids selected from citric, acetic, malic, and carbonic acids, fruit acids, and mixtures thereof, for the manufacture of a medicament for external use intended for the prevention or treatment of age spots. 3. The use according to claim 1 or 2, characterized in that the drug is a gel or emulsion. 4. The use according to claim 1 or 2, characterized in that the drug contains a pharmaceutically acceptable form of selenium in the form of selenite and is a gel or emulsion with a pH of less than 7.0, preferably less than 5.0, in particular 3.0-2, 5, and also this agent contains a pharmaceutically acceptable acid selected from citric, acetic, malic and carbonic acids, fruit acids and mixtures thereof.